Apparatus and method for analyzing patient tolerance to a stimulation mode favoring a spontaneous atrioventricular conduction

ABSTRACT

An implantable cardiac prosthesis device conducting an analysis of a patient tolerance to a pacing mode favoring the spontaneous atrioventricular conduction is disclosed. The device operates in a dual chamber (DDD or biventricular) mode and in a pacing mode favoring the spontaneous atrioventricular conduction such as an AAI mode ( 10 ) with a ventricular sensing or a mode with hysteresis of the atrioventricular delay. The device controls ( 10 - 18 ) the conditional switching from one mode to the other. The device comprises a hemodynamic sensor, including an endocardial acceleration sensor, derives a hemodynamic index representative of the hemodynamic tolerance of the patient to the spontaneous atrioventricular conduction. The device controls inhibiting or ( 20 ) forcing the conditional switching of the device to the DDD (or biventricular) mode according to the evolution of the hemodynamic index.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of and priority to FrenchPatent Application No. 0953982, filed Jun. 15, 2009.

FIELD OF INVENTION

The present invention is directed to an “active implantable medicaldevice” as defined by the 20 Jun. 1990 Directive 90/385/EEC of theCouncil of the European Communities, including implantable cardiacprosthesis devices such as cardiac pacemakers, defibrillators and/orcardioverters that continuously monitor a patient's heart rhythm anddeliver, if necessary, at the patient's heart electrical stimulation,resynchronization, cardioversion and/or defibrillation pulses in case ofa rhythm disorder detected by the device, and more particularly thosedevices that include circuitry for stimulation and detection in both theatrium and ventricle.

BACKGROUND

The basic mode of operation of an active implantable medical deviceknown as a cardiac prosthesis device is an AAI mode—or more precisely‘pseudo-AAI mode’—with single chamber atrial pacing (AAI mode in thestrict sense) and monitoring of ventricular activity. This mode isnormally maintained as long as an atrioventricular conduction is normal,i.e., as long as each atrial event (e.g., atrial detection correspondingto spontaneous activity, atrial pacing corresponding to a stimulation)is followed by an associated ventricular detection.

However, when the device operates in a “dual chamber” mode, after anatrial event—whether it is a spontaneous atrial depolarization(detection of a P wave) or stimulated atrial depolarization (delivery ofan A pulse)—the device simultaneously monitors ventricular activity andstarts measuring a delay called “atrioventricular delay”, commonlyreferred to as AVD. If at the end of the AVD, no spontaneous ventricularactivity (R wave) is detected, then the device triggers a stimulation ofthe ventricle (application of a V pulse).

Recent clinical studies have demonstrated that for preventing anoccurrence of heart failure or atrial fibrillation among patients withdual chamber pacemakers, it is recommended to avoid as much as possibleright ventricular pacing. This is done to preserve an intrinsic AVconduction in patients who have otherwise no permanent conductiondisorder requiring the use of a permanent ventricular pacing.

In this respect, recent cardiac prosthesis devices implemented a newstimulation mode that emphasizes a spontaneous ventricular conduction,and permits an operation with a long AVD that increases the time inwhich a potential spontaneous ventricular conduction may occur—but inreturn accepts the risk of maintaining the symptomatically long AVD.

Some pacemakers, for example, of the type described in EP 0 488 904 andits US counterpart U.S. Pat. No. 5,318,594 (ELA Medical, now known asSorin CRM) are equipped with AVD hysteresis algorithms that are used ina DDD mode to stimulate patients not having conduction disorders. Thesedevices can operate in two modes, DDD or AAI (the AAI mode being a DDDmode modified by lengthening the AV delay), and are provided with a modecalled “DDD-CAM” providing automatic mode switching (CAM) of DDD to AAIand vice versa. The value of the AVD is not fixed but varies linearlybetween a maximum value, used when the heart rate is near the restfrequency, and a minimum value, used when the heart rate is near itsmaximum value. The details of this adaptation of AVD is described forexample in EP 1 059 099 A and its US counterpart U.S. Pat. No. 6,622,039(ELA Medical, now known as Sorin CRM). The basic idea of the AVDhysteresis algorithm is to extend the value of AVD under certaincriteria, to which favors the occurrence of a potential spontaneousrhythm: the AVD can thus be lengthened to avoid unnecessary ventricularpacing or gradually reduced if no spontaneous rhythm is found, to returnto a normal value of conventional DDD stimulation.

This technique preserves the natural conduction in some patients, buthas been found to be of a limited use in other patients especially thosewith sinus dysfunction because the limits of the hysteresis make itdifficult to discover the spontaneous rhythm.

To overcome this limitation, a new pacing mode called “AAIsafeR” hasbeen developed in more recent devices, whose basic principle isexplained in EP 1 346 750 and its US counterpart U.S. Pat. No. 7,164,946(ELA Medical, now known as Sorin CRM). In an AAIsafeR mode, the deviceoperates in an AAI mode and the ventricular activity is constantlymonitored to detect an occurrence of atrioventricular blocks (AVB) thatcause a temporary disorder of depolarization of the ventricle. In thiscase, because a number of conditions are met, the device automaticallyswitches to a DDD mode, with operating parameters optimized for thistemporary AVB condition. In a multisite device, the switching is insteadmade to a biventricular stimulation mode (also referred to as a “BiV”mode), named “AAISafeRR”. After the AVB condition disappeared, and thusthe atrioventricular conduction was restored, the device automaticallyreturns to the AAI mode when a number of other conditions are met. TheAAIsafeR (or AAISafeRR) mode also includes a switching criterion linkedto the detection of an AV block of the first type or AVB1, that is tosay, the presence of a too long AVD: when the device detects, forexample, more than six consecutive cycles of a too long AVD (typicallylonger than 350-450 ms), then the device switches to a DDD mode, or in asimilar way, to a biventricular mode on a multisite device.

The AAIsafeR (or AAISafeRR) mode preserves the natural conduction veryefficiently, and the clinical results show a percentage of residualventricular pacing close to zero. Various improvements have been made,for example, to eliminate an incidence of premature ventricularcontractions (See EP 1 470 836 and its US counterpart U.S. Pat. No.7,076,297 (ELA Medical, now known as Sorin CRM)) and/or paroxysmal AVblock (See EP 1 550 480 A and its US counterpart U.S. Pat. No. 7,366,566(ELA Medical, now known as Sorin CRM), or in the presence of ventricularevents of uncertain nature occurring during the safety window (See EP 1731 195 A and its US counterpart U.S. Published Application No.2007/0135849. ELA Medical, now known as Sorin CRM), or in the presenceof ventricular tachycardias (See EP 1 731 194 A and its US counterpartU.S. Publication No. 2007/0135850, ELA Medical, now known as Sorin CRM).

One of the peculiarities of the AAIsafeR (or AAISafeRR) pacing mode isto allow a very long AVD, which is programmable. But such delays can bemore or less well tolerated by the patient, or can be tolerated undercertain conditions (e.g., at rest) and less tolerated in others (e.g.,during exercise). In patients suffering from brady-tachycardia andtaking anti-arrhythmic drugs, an appearance of symptoms related to a toolong AVD in AAI mode were notably reported.

In some patients, the risk of stimulating the right ventricle too oftenmust be balanced with the risk of developing symptoms by the use of atoo long AVD. In the absence of specific criteria, this risk is assessedas a function, for example, of the patient's ejection fraction, andpossibly based on symptoms reported at follow-up visits, but, in anyevent, is never based on the instantaneous situation of the patient.

Moreover, these difficulties linked to a too long AVD time may be onlytransient and only occur, for example, during certain patient activity,or only for some patients during atrial pacing and not after aspontaneous P wave. In such cases, it would be detrimental topermanently program a short AVD to overcome these transients.

It is therefore, an object of the present invention to provide a cardiacprosthesis device equipped with a pacing mode favoring a spontaneousconduction of a patient (including a device of the AVD hysteresis typeor a device of the AAIsafeR (or AAISafeRR type), which overcomes thedifficulties and limitations outlined above, related to considered along AVD in case of AVB1.

SUMMARY

Broadly, the present invention is directed to the use of an hemodynamicsensor, typically (but not limited to) an endocardial acceleration (EA)sensor to monitor and assess the patient's tolerance to a long AVD, soas to determine if the intrinsic conduction is tolerated or not, anddepending on the result of this assessment change the criteria to switchto a DDD mode (or to a BiV mode in multisite devices). This is done tomaximize the chances of maintaining a spontaneous ventricular conductionas long as it is tolerated by the patient, while minimizing the risk ofallowing a symptomatically long AVD.

More specifically, in terms of cardiac mechanics, the AVD must be longenough to allow a complete contraction of an atrium and thereby emptythe blood contained by the atrium into a ventricle, and a ventricularcontraction once the atrial contraction is fully completed. But theventricular contraction should not occur too long after, as a too longAVD could dissociate the atrium/ventricle system, with the risk oftriggering arrhythmias by a retrograde conduction, or reducing thehemodynamic effectiveness of the cardiac cycle. Indeed, as the atrialcontraction completes the ventricular filling, the delay between the endof the filling and the onset of the ventricular emptying is “lost” time,from a hemodynamic point of view. In addition, any extended period ofAVD impacts the ventricular diastole (ventricular filling post-emptying)and delays the end of this ventricular filling, which then overlaps thenext atrial contraction. It is therefore important to better adapt theAVD for each patient, so that the onset of ventricular emptying (causedby the stimulation of the ventricle) occurs immediately after thefilling of the ventricle by the atrium.

Hemodynamic sensors are distinguished from activity sensors (e.g.,accelerometers) and metabolic sensors (e.g., minute ventilation sensors)that are used for diagnosing the presence or absence of an exercise bythe patient and for quantifying its metabolic needs, for example, toadapt the heart rate of stimulation according to the detected level ofeffort or activity.

Hemodynamic sensors such as endocardial acceleration sensor orbioimpedance sensor, may not only monitor the patient effort as theactivity and/or metabolic sensors described above, but also give anindication of the patient's hemodynamic tolerance in relation with acertain event (e.g., ventricular arrhythmia), with drugs, or possiblywith a modification of the AVD.

U.S. Pat. No. 5,549,650 (Bornzin, et al./Pacesetter, Inc.) describes apacemaker comprising a hemodynamic sensor, designed to adapt a value ofAVD. The technique described therein is only intended to modify so as tooptimize the value of AVD according to the patient response. The objectof the present invention is instead to use the hemodynamic sensor not(or not only) for controlling the value of a long AVD, but also tocontrol the switching to a DDD (or BiV) mode: either by faster switchingto the DDD (or BiV) mode if the value of the long AVD is—from anhemodynamic point of view—not well tolerated by the patient or,conversely, to inhibit the switching to the DDD (or BiV) mode tomaintain the conduction if the long AVD is well tolerated. In a similarway, for a multisite device, the present invention regulates theswitching to a biventricular mode.

One aspect of the present invention is directed to an active implantablemedical device for cardiac stimulation, resynchronization and/ordefibrillation, comprising: means for detecting spontaneous atrial andventricular events; means for delivering ventricular and atrial pacingstimulation pulses; means for operating the device in a DDD and/or abiventricular mode with ventricular sensing and ventricular pacing inthe absence of spontaneous ventricular depolarization detected after anatrioventricular delay, and means for mode switching, to conditionallycontrol, according to predetermined criteria, the switching of thedevice between the DDD (or BiV) mode and a pacing mode emphasizing thespontaneous atrioventricular conduction and inversely back to the pacingmode from the DDD (or BiV) mode.

Preferably, the device of the invention includes a hemodynamic sensorhaving an output signal, means for deriving from the output signal ahemodynamic index representative of the patient's tolerance to aspontaneous atrioventricular conduction, and means for inhibiting, orfor forcing, said switching of the device to the DDD (or BiV) mode basedon said hemodynamic index.

The pacing mode favoring the spontaneous atrioventricular conduction tothe DDD (or BiV) mode preferably is either an AAI mode with ventricularsensing, or a DDD (or BiV) mode with hysteresis of the AVD.

According to an advantageous embodiment of the present invention, thedevice optionally comprises diagnostic means for determining anoccurrence of an atrioventricular block, and means for inhibiting, orfor forcing the switching of the device to the DDD (or BiV) mode, thediagnostic and inhibiting means being selectively activated only in theabsence of an atrioventricular block detected by the diagnostic means.

In another embodiment, the device comprises means for evaluating acurrent value of the AR interval separating an atrial pacing from theconsecutive spontaneous ventricular depolarization, means for comparingthe current value of the AR interval to a first threshold, means forinhibiting or forcing the conditional switching of the device to the DDD(or BiV) mode, said evaluating, comparing, and inhibiting means beingselectively activated only if the current value of the AR interval isgreater than the first threshold. In this case, the first threshold is avariable threshold, for example, depending on the heart rate, and thedevice further comprises means for dynamically reducing the value of thefirst threshold when the current heart rate is increased.

Yet another embodiment of the present invention provides that the devicefurther comprises means for detecting a state of patient effort; whereinthe means for inhibiting or forcing the switching of the device to DDD(or BiV) mode, in response to having forced a switch to DDD (or BiV)mode, inhibits the return to the pacing mode favoring the spontaneousatrioventricular conduction as long as the device detects a state ofpatient effort.

In a preferred embodiment, the means for inhibiting or forcing, theswitching of the device to the DDD (or BiV) mode operates to compare thecurrent value of the hemodynamic index to a reference hemodynamic index,and to force the device to switch to the DDD (or BiV) mode when thecurrent value of the index is less than the reference hemodynamic index.In this case, the value of the reference hemodynamic index is a variablevalue depending on the heart rate. The device further comprises meansfor dynamically increasing the value of the reference hemodynamic indexwhen the current heart rate is increased. More preferably thisparticular value controllably varies between a minimum and a maximumlimit. The device further comprises means for dynamically updating saidminimum and maximum limits.

In another embodiment of the present invention, the device comprisesdiagnostic means for determining an appearance of a permanentatrioventricular block, such that the value of the reference hemodynamicindex is forced to a value independent of the heart rate in the presenceof an atrioventricular block detected by the diagnostic means.Preferably, the hemodynamic sensor is one of an endocardial accelerationsensor or an epicardial acceleration sensor, a myocardium wall motionsensor, an intracardiac pressure sensor, an intracardiac bio-impedancesensor, an optical sensor for measuring oxygen saturation, or a sensorfor measuring volume change by ultrasound. In the case of an endocardialaccelerometer delivering a signal representative of the movementsproduced by cyclical contractions of the myocardium, the device includesmeans for recognizing and isolating in the signal emitted by the sensora component corresponding to a peak of endocardial accelerationassociated with the ventricular contraction, and for deriving saidhemodynamic index based on the amplitude of said component. In analternative implementation, the device includes means for recognizingand isolating in the signal delivered by the sensor at least twocomponents corresponding to two respective peaks of endocardialacceleration associated to the ventricular contraction, and for derivingsaid hemodynamic index from a time interval separating these twocomponents.

In the context of the present invention, it should be understood thatthe term “dual chamber” mode is intended to mean a pacing mode thatprovides atrial sensing and atrial stimulation, and ventricular sensingand ventricular stimulation, and thus broadly includes both an operationin a DDD mode for a conventional dual chamber cardiac prosthesis, and aBiV mode for a multisite cardiac prosthesis device.

BRIEF DESCRIPTION OF THE DRAWINGS

Further features, advantages and characteristics of the presentinvention will become apparent to a person of ordinary skill in the artin view of the following detailed description of preferred embodimentsof the invention, made with reference to the drawings annexed, in whichlike reference characters refer to like elements.

FIG. 1 is a series of two timing diagrams illustrating an exemplaryelectrocardiogram (ECG) of a patient and the corresponding endocardialacceleration (EA) signal, collected during a series of successive heartcycles, for a patient with paroxysmal AVB1;

FIG. 2 a shows the linear relationship linking the reference value ofthe index EA to the heart rate;

FIG. 2 b shows the linear relationship linking the threshold of the ARinterval beyond which the device evaluates the hemodynamic tolerance, tothe heart rate.

FIG. 3 is a flowchart of the operation of a pacemaker of the AAIsafeRtype in accordance with the present invention;

FIG. 4 is a flowchart of an algorithm for monitoring the hemodynamictolerance according to the present invention;

FIG. 5 is a flowchart of the reference values learning algorithm usedfor hemodynamic monitoring in accordance with the present invention; and

FIG. 6 is a series of two timing diagrams illustrating an exemplary ECGof a patient and the corresponding EA signal, collected during a seriesof successive cardiac cycles, in the case of a patient with a permanentAVB1.

DETAILED DESCRIPTION OF THE INVENTION

Examples of implementation of the present invention will now bedescribed with reference to the drawings FIGS. 1-6.

Regarding the software-related aspects of the present invention, thefunctionality and processes of the present invention may be implementedby an appropriate programming of the software of a known implantablepulse generator, for example, a pacemaker or defibrillator/cardioverter,comprising means for acquiring a signal provided through endocardialleads and/or various sensors monitoring the status of the patient.

In one embodiment, the present invention is applied to the commercialimplantable devices marketed by Sorin CRM, Clamart France, such as Replyand Paradym brand devices and comparable commercial and/or proprietarydevices of other manufacturers. These devices are equipped withprogrammable microprocessors, including circuits intended to acquire,format and process electrical signals collected by implanted electrodesand various sensors, and deliver pacing (stimulation) pulses toimplanted electrodes. It is also possible to upload towards thesedevices, by telemetry, pieces of software (i.e., a software controlmodule) that are stored in internal memory and run so as to implementthe intended features and functionality of the present invention, asdescribed herein. Implementing the features of the present inventioninto these devices is believed to be easily feasible by a person ofordinary skill in the art, and will therefore not be described in detailin this document.

The present invention is particularly applicable to a device such as apacemaker or defibrillator equipped with an algorithm to preserve aspontaneous conduction (e.g., an algorithm of the AAIsafeR type or analgorithm with hysteresis of the DDD-CAM type) and one or more physical(e.g., accelerometer G) and/or physiological (e.g., minute ventilationMV) sensors to distinguish periods of patient activity (e.g., exerciseor effort) from periods of patient rest.

In one embodiment, the device of the present invention further includesa hemodynamic sensor for estimating changes in contractility, correlatedwith increases in blood pressure. The hemodynamic sensor may be anendocardial acceleration sensor of a Peak Endocardial Acceleration (PEA)type as described, for example, in EP0515 319 (US counterpart, U.S. Pat.No. 5,304,208), EP0582162 (U.S. counterpart U.S. Pat. No. 5,454,838) orEP0655260 (US counterpart U.S. Pat. No. 5,496,351) (all three assignedto Sorin Biomedical Cardio SpA. EP0515 319 (US counterpart U.S. Pat. No.5,304,208) describes how to collect an endocardial acceleration (EA)signal using an endocardial lead equipped with a distal electrode ofstimulation implanted to the apex of the ventricle, also incorporating amicro-accelerometer to measure the endocardial acceleration. EP0655260(US counterpart U.S. Pat. No. 5,693,075) describes a method to processthe measured EA signal to derive two values of peak endocardialacceleration corresponding to the two major noises recognizable in eachcycle of a healthy heart.

More specifically, the first peak endocardial acceleration (“PEA1”)corresponds to the closure of the mitral and tricuspid valves, at thebeginning of an isovolumetric ventricular contraction (systole). Thevariations of this first peak PEA1 are closely related to the pressurechanges in the ventricle, therefore is a parameter representative of themyocardial contractility. The amplitude of the first peak PEA1 is, moreprecisely, correlated with the positive maximum pressure change dP/dt inthe left ventricle.

The second peak of endocardial acceleration (“PEA2”) corresponds to theclosure of the aortic and pulmonary valves at the phase of anisovolumetric ventricular relaxation. This second peak PEA2 is producedby the sudden deceleration of the blood mass in motion in the aorta, andtherefore is a parameter representative of the peripheral blood pressureat the beginning of the diastole.

Alternatively, the hemodynamic sensor may be a sensor of intracardiacimpedance, such as a sensor for measuring bioimpedance (BioZ), forexample, the one disclosed in EP1 116 497 (US counterpart U.S. Pat. No.6,604,002) or EP1 138 346 (US counterpart U.S. Pat. No. 6,725,091) (bothin the name ELA Medical, now known as Sorin CRM). Specifically,EP1116497 (US counterpart U.S. Pat. No. 6,604,002) describes a method toperform a dynamic measurement of a bioimpedance signal to assess thediastolic and systolic volumes, and thus obtain an indication of thecardiac output and thus of the ejection fraction. This documentdescribes in particular a technique for measuring a transvalvularbioimpedance (an impedance between the atrium and the ventricle locatedon the same side of the heart) by a tripolar configuration, withinjection of a current pulse between an atrial site and a ventricularsite, and collection of a differential potential between the atrial siteand the ventricular site, with one of these sites common to theinjection and the collection, a dedicated site of injection and adedicated site of collection. The injected current is of a lowmagnitude, insufficient to excite the heart cells.

EP1138346 (US counterpart U.S. Pat. No. 6,725,091) describes anothertype of bio-impedance measurement, namely a transeptal bioimpedance, animpedance between a site located on one side of the heart and a site onthe other side of the heart. This technique also helps deliver a signalrepresentative of the ejection fraction, although the signal is weakerthan a transvalvular bioimpedance signal, and it is also influenced bythe impedance of the septum tissues.

In the following description of the examples describing an endocardialacceleration sensor, it should be understood that these teachings aretransferable to other types of acceleration sensors, e.g., an epicardialsensor or a sensor of wall motion of the myocardium, or generally anyother type of sensor delivering a signal representative of thehemodynamic behavior of the myocardium, such as an intracardiacbioimpedance sensor or a pressure sensor. These sensors are designed toassess the hemodynamic tolerance of the patient to a long AVD not onlyto adjust the value of the AVD, but also to switch more quickly to a DDDmode if the value is not well tolerated, or, conversely, to preserve theintrinsic conduction and prevent or delay the switching to the DDD modeif the AVD is hemodynamically tolerated.

A long AVD is a situation characteristic of a potential AVB1.Specifically, a first-degree AV block or AVB1 corresponds to a present,but delayed conduction. It is distinguished from: (i) the second degreeAVB (AVB2), which is characterized by an incomplete conduction with agradual lengthening of the PR (or AR) interval so that a part of the Pwaves is no longer conducted; (ii) the complete AV block or third degreeAVB (AVB3) which is manifested by completely blocked atrial waves(stimulated or spontaneous), in other words atrial events that are notfollowed by a ventricular depolarization, and (iii) the ventricularpause, when the interval separating two ventricular events exceeds aspecified period, e.g., more than three seconds, or when the ventricularpause is not originated from a disorder of the atrioventricularconduction.

An AVB1 may be paroxysmal or permanent. A paroxysmal AVB1 isintermittent, and typically occurs during phases of sleep or stress, andspontaneously disappears at the end of effort or during wake-up. Incontrast, a permanent or quasi-AVB reveals a chronic disorder that mustbe adequately taken into account.

Implementation of the Invention in Case of a Paroxysmal AVB1

With reference to FIG. 1, the upper timing diagram illustrates anendocardial electrocardiogram (ECG) with, for each cardiac cycle, astimulated atrial wave A, followed by a spontaneous ventriculardepolarization wave R. In the first cycles, the delay AR1 betweenstimulation A and detection R is shorter than the delay AR2 in a latercycle, indicating an increased intrinsic conduction AV delay. The lowertiming diagram provides a hemodynamic signal, typically the endocardialacceleration (EA) signal corresponding to the ECG signal in the upperdiagram. In the example shown, the chosen representative parameter isthe amplitude EA1, EA2 . . . of the EA signal at the instant of the QRScomplex, that is to say, the first peak of endocardial acceleration PEA1corresponding to the first major noise at the beginning of the phase ofan isovolumetric ventricular contraction. It is known that the amplitudevariations of the first peak PEA1 are closely related to changes inpressure in the ventricle and therefore is a parameter representative ofthe myocardium contractility. The dashed line indicates a referenceamplitude EA_(ref) to differentiate a good hemodynamic tolerance (e.g.,EA1>EA_(ref)) and a poor hemodynamic tolerance (e.g., EA2<EA_(ref)).

Thus it can be seen that for the delay AR1 the amplitude EA1 beinggreater than the reference value indicates that the delay AR1 istolerated, thus does not require any special action of the device orchange in mode. In contrast, for the AR2 which is a longer delay thanthe AR1, the corresponding amplitude EA2 is less than the referencevalue EA_(ref): This indicates that the delay AR2 is not tolerated, thusrequires ventricular pacing to prevent symptoms related to AVB1.

The principle of the present invention is to use the correlation betweenAVD and the peak amplitude of the signal (e.g., EA and/or of otherrelevant parameters such as the amplitude of the second peak, theinterval between the first and second peak) as an index or marker ofhemodynamic tolerance of the patient to a long AVD.

This index or marker is designated Indice_EA. A reference hemodynamicindex value is defined by averaging the hemodynamic index at rest andduring exercise, for normal values of AVD, that is to say in the absenceof an AVB1 (i.e., for values of AVD below a threshold value, hereinafterreferred to as MaxARhemo beyond which the hemodynamic tolerance isassessed). The reference hemodynamic index value thus determined is avariable depending on the patient's activity, for example, a linearvariation between a value at rest and a value during effort. Once thisreference value is set, and when a long AVD is experienced (the delay ARis above the threshold MaxARhemo), the device compares the current indexto the reference index. For convenience, the term “index” isexchangeably used to refer to the “hemodynamic index”.

If the current index is less than the reference index, the deviceconsiders that there is no hemodynamic tolerance and that the patient isconsidered to experience or is at the risk of having a symptomatic AVB1.In this case, it is necessary to stimulate the ventricle to recover asatisfactory hemodynamic situation. The device then switches to a DDDmode (in the case of an AAIsafeR or equivalent device) or shortens theAVD (in the case of a device with hysteresis of the AVD). In thefollowing description of the present invention, it should be understoodthat by switching to a DDD mode also represents switching to a BiV modein the case of a multisite device. The device remains in the DDD modefor a predetermined period and/or until the end of the situation ofeffort, then switches back to the AAI mode (or extends again the AVD inthe case of a device with hysteresis). Otherwise, the device considersthat the intrinsic conduction is tolerated by the patient, and forcesthe device to remain in the AAI mode (or inhibits the shortening of theAVD in the case of a device with hysteresis).

The procedure for operating the device depending on the hemodynamicindex is now described in more detail, with reference to FIGS. 2 to 5.

FIG. 2 a illustrates the relationship between the reference value ofEA_(ref), the Indice_EA_ref_encours, and the heart rate Fc. For somechoice of the hemodynamic index, the reference value is fixed and theamplitude of the first peak of the signal EA (PEA1) is chosen, thus itis desirable to modify the threshold value EA_(ref) depending on thelevel of effort. As the amplitude of the first peak of the EA signalincreases when the heart rate increases, it is logical to adapt thethreshold value EA_(ref).

As shown in FIG. 2 a, this index EA_(ref) varies linearly between aminimum value (designated Indice_EA_ref_repos), corresponding to a heartrate near the base rate F_(base), and a maximum value (designatedIndice_EA_ref_exer) used when the heart rate is close to the maximumheart rate F_(max). Between these two extremes, each instantaneous heartrate value F of the heart rate F_(c) corresponds to an instantaneousvalue of the reference index EA_(ref) designated Indice_EA_ref_encours.It is noted that the linear relationship is chosen for its simplicity,but this relationship is not limited to a linear relationship and otherindexes or other types of hemodynamic sensors may correspond to otherfunctional and non-linear relationships.

FIG. 2 b illustrates the relationship linking the threshold of the ARinterval beyond which the hemodynamic tolerance is analyzed, to theinstant heart rate F_(c). This threshold value, designated MaxARhemo, isthe limit delay AR beyond which the device considers that the patientexhibits or is at risk of AVB1. Therefore, beyond the limit delay AR itis necessary to analyze the hemodynamic tolerance to the long AR delay.In a simplified implementation, this value may be fixed, for example, ata value in the range between about 400 or 450 ms. However, even if thefixed value is well adapted to a condition of rest, it may be inadequateduring an effort: the physiological PR interval is shortened when heartrate increases, so a period of 300 ms may be acceptable in a state ofrest, but it is much too long in a situation of an effort.

As illustrated in FIG. 2 b, the device varies the limit delay MaxARhemobetween a maximum value (designated MaxARhemo_max) applied when theheart rate F_(c) is close to the base rate F_(base), and a minimum value(designated MaxARhemo_min) when the heart rate F_(c) is near the maximumheart rate F_(max), preferably according to a linear function. Inbetween each of these heart rates corresponds to an instantaneous valueF_(c) of the limit delay MaxARhemo beyond which the hemodynamictolerance of the AVB1 is assessed.

FIG. 3 is a chart illustrating an implementation of the presentinvention within a device comprising an operating mode of the AAIsafeRtype. This implementation is applicable mutatis mutandis to a deviceusing an algorithm of adaptation of the hysteresis of the AVD.

The device operates in an AAI mode (block 10). The routine waits (block12) for the completion of the ventricular cycle that is underway toanalyze the state of conduction. The routine evaluates (block 14) if thecriteria for suspected AVB1, AVB2 or AVB3 (or other criteria) aresatisfied. These criteria are, for example:

-   -   (a) first-degree AVB or AVB1 (conduction present but delayed):        the number of atrial events followed by a ventricular detection        occurs, for example, after a period of more than 350 ms (for a        spontaneous atrial event) or 450 ms (for a stimulated atrial        event) exceeding a given number, e.g., six consecutive cardiac        cycles;    -   (b) second-degree AVB or AVB2 (incomplete conduction, the        gradual lengthening of the PR interval, or AR, such that a part        of the P waves is no longer conducted): the number of atrial        events not followed by a ventricular detection exceeds a certain        number over the duration of a monitoring window extending over a        predetermined number of atrial events: for example, when the        device detects three non-consecutive blocked P waves among the        twelve last cardiac cycles; and    -   (c) complete AVB, third degree, or AVB3 (atrial waves,        stimulated or spontaneous, totally blocked, that is to say, no        longer followed by a ventricular depolarization): for example,        succession of two atrial waves detected or stimulated, blocked        or more than three seconds without any ventricular detection        (situation of ventricular pause).

If any of these criteria (or other criterion) is verified, the algorithmswitches the device into a DDD mode (block 16) in accordance with anAAIsafeR mode of operation.

However, if none of the detection criteria for AVB1, AVB2 and AVB3 issatisfied, the algorithm evaluates the length of the last N AR delays(block 18). According to a preferred embodiment, this assessment maycorrespond to the calculation of a mean value, in search of a maximumvalue within the N AR delays, or as in the present example, to theestablishment of a criterion based on exceeding N consecutive AR delaysof the instantaneous value of the threshold MaxARhemo, said MaxARhemothreshold being chosen so as to always be less than the threshold of atraditional AVB1 test (e.g., 350 or 450 ms).

If this criterion is satisfied, the patient is not experiencing AVB1under the traditional criteria but is experiencing AVB1 against the testin accordance with the present invention. The algorithm then, accordingto the present invention, assesses the patient's tolerance to that AVB1by triggering a monitoring of the hemodynamic tolerance (block 20, whichwill be discussed in detail with reference to FIG. 4). This occursduring the phase of monitoring of the hemodynamic tolerance that thealgorithm forces the device to stay in an AAI mode, or otherwise imposesa switch to a DDD mode, depending on the result of the analysis of thehemodynamic tolerance.

If, however, the test evaluated in block 18 is not satisfied, thepatient is not experiencing AVB1, thus no specific action is taken, andthe algorithm returns to block 12 to analyze the next cardiac cycle.

FIG. 4 is a flowchart describing in detail how the follow-up of thehemodynamic tolerance is made corresponding to block 20 of FIG. 3 in asituation of AVB1 and in the presence of AR delays greater than thethreshold value MaxARhemo.

First (block 22), the algorithm compares the current value of the indexIndice_EA designated Indice_EA_encours, measured from the hemodynamicsensor, to the instantaneous reference value, Indice_EA_ref_encours. Ifthe current index is greater than or equal to the reference value, theAVB1 is considered to be tolerated. There is no need to switch to a DDDmode and the algorithm returns (block 24) in block 12 of FIG. 3.

Otherwise, the algorithm switches to a DDD mode (block 26), withpossible hysteresis to maintain a sufficient margin corresponding, forexample, to the physiological variation in the signals.

In block 28, a counter is reset, which allows to maintain the DDD modefor a predetermined number of cycles. The counter is programmable tocount, for example, 100 cardiac cycles.

In block 30, the algorithm waits until the next ventricular complex toupdate the data corresponding to the time spent in the DDD mode. Inblock 32, the counter is compared to the predefined value mentionedabove (for example, 100 cardiac cycles). If this value is not reached,the device remains in the DDD mode, the counter is increased by one unit(block 34) and the algorithm returns to block 30.

Otherwise, the algorithm tests (block 36) whether the patient is in aphase of rest or exercise using the activity sensor of the device. Ifthe patient is not at rest, then the device is held in the DDD modeuntil detection of a rest phase for the patient (back to block 30).Indeed, in patients with sinus dysfunction, the effort is one of themain factors triggering AVB1, so it is desirable to keep the DDD modethroughout an effort to optimize the tolerance during this phase.

Otherwise, when a rest condition is diagnosed at block 36, then thealgorithm switches again the device in the AAI mode (block 38) andreturns (block 40) in block 12 of FIG. 3 waiting for the next cycle.

FIG. 5 illustrates an exemplary flow chart for updating the referencevalues of the hemodynamic sensor. In one embodiment, this update is runin parallel to the procedures described above, and is executed when thedevice is in AAI mode, in the absence of detection of an AVB1. Inanother embodiment, the update procedure for the reference value is runindependently by a separate algorithm, and the updated reference valueis provided to the algorithm executing the procedures in FIGS. 3 and 4.

As explained above with reference to FIG. 2 a, the reference indexEA_(ref) is adjustable between a minimum value Indice_EA_ref_repos and amaximum value Indice_EA_ref_exer. The current valueIndice_EA_ref_encours varies between these two extremes. Initially, thealgorithm waits until the end of the ventricular cycle underway toconduct the analysis (block 42). It then compares (block 44) the currentAR delay to the current threshold MaxARhemo. If the AR delay exceeds thecurrent threshold MaxARhemo, this means there is a situation of AVB1,and the reference data are not updated (as noted above, this update ismade in the absence of detection of AVB1). The algorithm then returns toblock 42 and waits for the next cycle.

In the absence of AVB1 when the AR delay does not exceed the currentthreshold MaxARhemo, the update procedure starts. First, the algorithmtests (block 46) if the patient is at rest or during exercise. If thepatient is determined to be at rest, the algorithm includes in theoverall calculation of Indice_EA_ref_repos the current value ofIndice_EA_encours (block 48). This calculation can be, for example, adaily average, but the minimum or maximum value found at rest over agiven period of time may be used for calculating and updating the valueof Indice_EA_ref_repos. If the patient is active, the algorithm updatesthe value of Indice_EA_ref_exer.

To this purpose, a value maxEA is initialized with the current value ofIndice_EA_encours (block 50). The algorithm is then put on hold untilthe next ventricular cycle (block 52) and compares again (block 54) thevalue of the delay AR to the current value of MaxARhemo, in the samemanner as in block 44. If the delay AR exceeds MaxARhemo, this meansthat there is a situation of AVB1, and the update of the reference valueis interrupted. Before completing the update, the algorithm comparesIndice_EA_ref_exer to maxEA (block 56). If maxEA is greater thanIndice_EA_ref_exer, the algorithm updates Indice_EA_ref_exer with thisnew value maxEA (block 58). Otherwise, the update is interrupted and thealgorithm returns to block 42 waiting for the next cycle.

If, at block 54, the value of the delay AR is less than the currentvalue of MaxARhemo, this means that there is no situation of AVB1, andthe update procedure continues.

The algorithm checks if the patient is returned to rest (block 60). Ifthis is the case, it terminates the update of the value of effort, andthe reference values are updated in blocks 56 and 58 as described aboveunder the condition of AVB1. In the opposite case (patient still inexercise), the algorithm compares (block 62) the value ofIndice_EA_ref_encours to the value of maxEA. If maxEA is less thanIndice_EA_ref_encours, the value of maxEA is updated with the new valueIndice_EA_ref_encours (block 50), otherwise no update of maxEA isnecessary and the algorithm waits (block 52) for the next cycle.

It is noted that the method described above provides for the referenceindex EA_(ref) an average value at rest for the lower limitIndice_EA_ref_repos, and the maximum value at effort for the upper limitIndice_EA_ref_exer. Such a system would deviate over the iterations, soin order to avoid drifting of these values, the parameter maxEA islowered by one increment at regular intervals (e.g. every 24 hours) torebalance the system.

Implementation of the Invention in Case of a Permanent AVB1

The procedures that have just been described above in reference to FIGS.3-5 are effective if the patient suffers from a paroxysmal AVB1,particularly in regard to learning of the reference values. In case of apermanent AVB1, however, it is impossible to update the index EA_(ref).

It is therefore necessary to choose another reference index derived fromthe EA signal, such as a filling time. The reference index in this caseis preferably a simple threshold value, which does not necessarily varywith heart rates F.

With reference to FIG. 6, in case of a permanent AVB1, the delays ARremain long while other conditions vary. For example, heart rate mayincrease resulting in a shortening of the RR interval (RR_(X)<RR_(y)).The parameter used to derive the EA signal is, for example, the delay ATseparating the two endocardial acceleration peaks PEA1 and PEA2 of theEA signal during one cardiac cycle. These peaks are identified bytemporal markers T_(1EA) and T_(2EA). The interval ΔT_(x) is compared toa reference threshold ΔT_(ref), and it is determined that AVB1 istolerated if ΔT_(x)>ΔT_(ref), and not tolerated otherwise. In the lattercase, the algorithm switches the device to the DDD (or BiV) mode, as thesituation of AVB1 requires the transition to this mode of stimulation.The rest of the operation, including the procedures to return to the AAImode, may be identical as in the previous case discussed above.

In one embodiment, the time markers T_(1EA) and T_(2EA) are determinedby implementing the technique described in European Application No. 09209116.1 of 18 Feb. 2009 (US counterpart U.S. Pat. Pub. No.2009/0209875), filed under priority of French application 08 00907 of 20Feb. 2008, entitled “Device for the analysis of endocardial signal ofacceleration”, (ELA Medical, now Sorin CRM). This document describes howto determine the temporal position of various components associated withthe heart sounds S1, S2, S3 or S4 of an EA signal of endocardialacceleration, including but not limited to, the components EA1 and EA2or to the two “peaks” of endocardial acceleration PEA1 and PEA2. Theinterval ΔT is continuously calculated, either in absolute terms or byits variations relative to a cardiac mechanical component such as thefilling time.

In FIG. 6, the patient is in a situation of AVB1, with a characteristicconstant delay PR. However, as the heart rate progressively increases,the RR delay decreases (RR_(y)<RR_(x)), with decreasing hemodynamicdelays (ΔT_(y)<ΔT_(x)). The threshold of tolerance T_(ref) is chosencorresponding to the minimum filling time ensuring a satisfactorycardiac hemodynamic situation.

In FIG. 6, initially ΔT_(x)>ΔT_(ref), which means that the AVB1 istolerated, and the device remains in the AAI mode. However, laterΔT_(y)<ΔT_(ref), which means that the filling time is insufficient. TheAVB1 is thus not tolerated by the patient and the device operates afall-back in the DDD (or BiV) mode (the subsequent return to the AAImode using the same procedures as those described with respect to FIG.4).

One skilled in the art will appreciate that the present invention can bepracticed by embodiments other than those described herein, which areprovided for purposes of illustration and not of limitation.

I claim:
 1. An active implantable medical device for stimulation,resynchronization and/or defibrillation of a patient, comprising: meansfor detecting spontaneous atrial and ventricular events; means fordelivering ventricular and atrial stimulation; means for detectingspontaneous ventricular depolarization after an atrial pacing; means formeasuring an atrioventricular delay between the atrial pacing and thecorresponding ventricular depolarization; means for operating the devicein a dual chamber mode with ventricular sensing and ventricular pacingin the absence of spontaneous ventricular depolarization detected afteran atrioventricular delay; means for mode switching, to controlconditionally, according to a predetermined criteria, the switching ofthe device between a dual chamber mode and a pacing mode favoring aspontaneous atrioventricular conduction; a hemodynamic sensor having anoutput signal; means for deriving from the output signal a hemodynamicindex representative of a patient's tolerance to the atrioventriculardelay, wherein the means for deriving utilizes output data from thehemodynamic sensor associated with a single cardiac cycle to derive thehemodynamic index, wherein the means for deriving the hemodynamic indexis configured to derive the hemodynamic index when the atrioventriculardelay exceeds a threshold value; and means for inhibiting or forcingsaid conditional switching of the device to the dual chamber mode basedon said hemodynamic index derived from the output data from thehemodynamic sensor associated with the single cardiac cycle.
 2. Thedevice of claim 1, wherein the pacing mode favoring the spontaneousatrioventricular conduction to the dual chamber mode comprises an AAImode having a ventricular detection.
 3. The device of claim 1, whereinthe pacing mode favoring the spontaneous atrioventricular conduction tothe dual chamber mode is one of a DDD mode and a biventricular modehaving hysteresis of the atrioventricular delay.
 4. The device of claim1, further comprising means for diagnosing an occurrence of anatrioventricular block, wherein the means for inhibiting or forcing saidconditional switching of the device to the dual chamber mode isselectively activated in the absence of atrioventricular block proved bythe means for diagnosing.
 5. The device of claim 1, further comprising:means for evaluating a current value of an interval between the atrialpacing and the consecutive spontaneous ventricular depolarization; andmeans for comparing said current value of the interval to the thresholdvalue, wherein the means for inhibiting or forcing the conditionalswitching of the device to the dual chamber mode is selectivelyactivated in response to the current value of the interval being greaterthan the threshold value.
 6. The device of claim 5, wherein thethreshold value comprises a variable threshold, depending on the heartrate of the patient, and the device further comprising means fordynamically reducing the value of the variable threshold when thecurrent heart rate is increased.
 7. The device of claim 1, furthercomprising means for detecting of a state of patient effort, wherein themeans for inhibiting or forcing of the conditional switching of thedevice to the dual chamber mode further comprises means for forcing aswitch to the dual chamber mode, and inhibiting a return back to thepacing mode favoring the spontaneous atrioventricular conduction untilthe device detects a state of patient effort.
 8. The device of claim 1,wherein the means for inhibiting or forcing the conditional switching ofthe device to the dual chamber mode further comprises means forcomparing the current value of the hemodynamic index to a referencehemodynamic index, wherein the means for forcing switches the device tothe dual chamber mode when the current value of the hemodynamic index isless than the reference hemodynamic index.
 9. The device of claim 8,wherein the value of the reference hemodynamic index is a variable valuedepending on the heart rate of the patient, and the device furthercomprises means for dynamically increasing the value of the referencehemodynamic index when the current heart rate is increased.
 10. Thedevice of claim 9, wherein the value of the reference hemodynamic indexis a variable value between a minimum limit and a maximum limit, and thedevice further comprises means for dynamically updating said minimum andmaximum limits.
 11. The device of claim 8, further comprising: means fordetermining an occurrence of a permanent atrioventricular block, andmeans for forcing the reference hemodynamic index to a value independentof the heart rate in the presence of a determined permanentatrioventricular block.
 12. The device of claim 1, wherein thehemodynamic sensor further comprises a sensor selected from among thegroup consisting of an endocardial acceleration sensor, an epicardialacceleration sensor, a myocardium wall motion sensor, an intracardiacpressure sensor, an intracardiac bioimpedance sensor, an optical sensormeasuring oxygen saturation, and a sensor for measuring a change involume by ultrasounds.
 13. The device of claim 12, wherein thehemodynamic sensor is a hemodynamic endocardial acceleration sensor,delivering the output signal representative of the movements produced bythe cyclical contractions of the myocardium.
 14. The device of claim 13,further comprising: means for recognizing and isolating in the outputsignal a component corresponding to a peak endocardial accelerationassociated with a ventricular contraction, and means for deriving saidhemodynamic index from said component.
 15. The device of claim 13,further comprising: means for recognizing and isolating in the outputsignal delivered by the hemodynamic sensor at least two componentscorresponding to two respective peaks of endocardial accelerationassociated with the ventricular contraction, and means for deriving saidhemodynamic index from a time interval separating the at least twocomponents.
 16. The device of claim 1, wherein said dual chamber modecomprises a DDD mode.
 17. The device of claim 1, wherein said dualchamber mode comprises a biventricular mode.
 18. The device of claim 1,wherein: said hemodynamic sensor comprises a hemodynamic endocardialacceleration sensor; said output signal is representative of movementsproduced by cyclical contractions of a myocardium; said means forderiving from the output signal a hemodynamic index is configured toderive said hemodynamic index from a component in the output signalcorresponding to a peak endocardial acceleration associated with aventricular contraction; and said means for inhibiting or forcing saidconditional switching of the device to the dual chamber mode isconfigured to determine whether to place the device in the dual chambermode based on the hemodynamic index derived from the component in theoutput signal corresponding to the peak endocardial accelerationassociated with the ventricular contraction.
 19. An implantable medicaldevice comprising: a hemodynamic sensor configured to generate an outputsignal, wherein the hemodynamic sensor comprises an electronic sensorconfigured to measure a value representative of a property of at leastone of heart tissue and blood flowing through a heart or blood vesselsproximate to the heart; and one or more circuits configured to: switchthe implantable medical device between a single chamber mode and a dualchamber mode, wherein, in the single chamber mode, the one or morecircuits are configured to stimulate the atrium and prompt spontaneousatrioventricular conduction, and wherein, in the dual chamber mode, theone or more circuits are configured to stimulate the ventricle in theabsence of spontaneous ventricular depolarization detected after anatrioventricular delay, measure the atrioventricular delay between anatrial pacing event and a spontaneous ventricular depolarization afterthe atrial pacing event, determine whether the atrioventricular delayexceeds a threshold atrioventricular delay, in response to theatrioventricular delay exceeding the threshold atrioventricular delay:derive from the output signal of the hemodynamic sensor a hemodynamicindex representative of a patient's tolerance to the atrioventriculardelay that exceeds the threshold atrioventricular delay, and determinewhether to activate or deactivate the dual chamber mode based on thehemodynamic index.
 20. The device of claim 19, wherein the singlechamber mode comprises an AAI mode having a ventricular detection. 21.The device of claim 19, wherein the hemodynamic sensor is configured tomeasure one or more of an endocardial acceleration value, an epicardialacceleration value, a myocardium wall motion value, an intracardiacpressure value, an intracardiac bioimpedance value, an oxygen saturationvalue, or a volume change value.
 22. An implantable medical devicecomprising: a hemodynamic sensor configured to generate an outputsignal; and one or more circuits configured to: switch the implantablemedical device between a single chamber mode and a dual chamber mode,wherein, in the single chamber mode, the one or more circuits areconfigured to stimulate the atrium and prompt spontaneousatrioventricular conduction, and wherein, in the dual chamber mode, theone or more circuits are configured to stimulate the ventricle in theabsence of spontaneous ventricular depolarization detected after anatrioventricular delay, determine, over a plurality of atrial events,whether an amount of atrial events that are not followed by a detectedventricular event exceeds a threshold, in response to the number ofatrial events that are not followed by a detected ventricular eventexceeding the threshold, activate the dual chamber mode, in response tothe number of atrial events that are not followed by a detectedventricular event not exceeding the threshold, determine whether toactivate or deactivate the dual chamber mode using the hemodynamicsensor by: deriving from the output signal of the hemodynamic sensor ahemodynamic index representative of a patient's tolerance to theatrioventricular delay when the atrioventricular delay exceeds athreshold value, and determining whether to activate or deactivate thedual chamber mode based on the hemodynamic index.